Education

Education/Training Program Affiliations

Biosciences Graduate ProgramInterdisciplinary Graduate Program in Molecular and Cellular Biology

Research Summary

Research in the Koland laboratory focuses upon the signaling events elicited by members of the epidermal growth factor (EGF) receptor family (ErbB/HER family receptors). ErbB family receptors are among a larger group of receptors possessing intrinsic protein tyrosine kinase activity that is activated upon binding of polypeptide growth factors. ErbB receptors and their associated growth factor ligands play crucial roles in human cancer, and in the context of breast cancer, they are important diagnostic markers and the targets of new therapeutic agents. The Koland laboratory is investigating ErbB receptor signaling in mammary tumor cells by use of biochemical and biophysical approaches. One research initiative addresses the molecular mechanisms by which the intracellular protein tyrosine kinase domain of the EGF receptor is regulated by binding of growth factor to the receptor extracellular domain. Here the laboratory has developed novel fluorescent spectroscopic methods by which structural changes associated with receptor activation and phosphorylation can be detected. With these methods Dr. Koland's laboratory has demonstrated that phosphorylation of the receptor C-terminal domain alters its conformation and effects its displacement relative to the catalytic site. These findings are consistent with a model in which the C-terminal phosphorylation domain in the basal state interacts with the catalytic core of the kinase to inhibit its activity. In this model, phosphorylation of the C- terminal domain induces structural changes that relieve this inhibitory interaction and result in kinase activation. A more recent initiative explores how ErbB family members are spatially organized in the cell membrane at the sub-light microscopic level, and how this spatial microorganization might be perturbed in cancer cells. Here the laboratory seeks to determine whether ErbB receptors are confined to membrane microdomains of specific biochemical composition and how membrane microenvironment impacts upon receptor signaling. Approaches used include fluorescence microscopy and electron microscopy (EM). Preliminary EM studies indicate that ErbB receptors are in breast cancer cell membranes indeed localized in submicroscopic domains consistent with the size of lipid rafts.

Kratz D,
Koland J.
Growth inhibition of fibroblasts expressing the ErbB3/HER3 receptor protein by heregulin-neutralizing antibody.
University of Iowa College of Medicine Research Week.
1997.

Vijapurkar U,
Koland J.
Mutation of a Shc binding site tyrosine residue in ErbB3/HER3 blocks activation of mitogen-activated protein kinase by the ErbB2/ErbB3 heregulin coreceptor.
University of Iowa College of Medicine Research Week.
1997.

Shinjo K,
Koland J,
Hart M,
Narasimhan V,
Johnson D,
Evans T,
Cerione R.
Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42..
Proceedings of the National Academy of Sciences of the United States of America.
1990 December. 87(24):9853-7.
[PubMed]